We have updated our privacy policy. If you have any question, contact us at privacy@scicrunch.org. Dismiss and don't show again

Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Ca(V)1.2 calcium channel dysfunction causes a multisystem disorder including arrhythmia and autism.

Cell | Oct 1, 2004

Ca(V)1.2, the cardiac L-type calcium channel, is important for excitation and contraction of the heart. Its role in other tissues is unclear. Here we present Timothy syndrome, a novel disorder characterized by multiorgan dysfunction including lethal arrhythmias, webbing of fingers and toes, congenital heart disease, immune deficiency, intermittent hypoglycemia, cognitive abnormalities, and autism. In every case, Timothy syndrome results from the identical, de novo Ca(V)1.2 missense mutation G406R. Ca(V)1.2 is expressed in all affected tissues. Functional expression reveals that G406R produces maintained inward Ca(2+) currents by causing nearly complete loss of voltage-dependent channel inactivation. This likely induces intracellular Ca(2+) overload in multiple cell types. In the heart, prolonged Ca(2+) current delays cardiomyocyte repolarization and increases risk of arrhythmia, the ultimate cause of death in this disorder. These discoveries establish the importance of Ca(V)1.2 in human physiology and development and implicate Ca(2+) signaling in autism.

Pubmed ID: 15454078 RIS Download

Mesh terms: Abnormalities, Multiple | Action Potentials | Animals | Arrhythmias, Cardiac | Autistic Disorder | Brain | Brain Chemistry | CHO Cells | Calcium | Calcium Channels, L-Type | Calcium Signaling | Cell Membrane | Child | Cricetinae | Female | Genetic Diseases, Inborn | Heart | Humans | Infant, Newborn | Limb Deformities, Congenital | Male | Mice | Mutation, Missense | Myocytes, Cardiac | Neurons | Oocytes | Pedigree | Syndrome | Xenopus laevis

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NHLBI NIH HHS, Id: HL52338
  • Agency: Telethon, Id: GP0227Y01
  • Agency: NIMH NIH HHS, Id: MH66398
  • Agency: NHLBI NIH HHS, Id: HL46401
  • Agency: NIDCD NIH HHS, Id: DC03610

Comparative Toxicogenomics Database (Data, Disease Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.